Proteomics

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Deciphering the impact of ectopic SNAI1 expression on renal tubular cell proteome and functions


ABSTRACT: Snail1 is crucial in regulating epithelial mesenchymal transition (EMT), which leads to excessive extracellular matrix (ECM) production and organ fibrosis including the kidney. Elucidating the roles of snail1 in EMT and kidney fibrosis is thus vital for developing targeted therapies. This study investigated the alterations in the proteome of SNAI1-overexpressed proximal tubular epithelial cells over the vector-transfected cells by label-free quantitative proteomics. Of 670 identified proteins, 233 showed significant changes due to ectopic snail1 expression. Of these, immunoblotting confirmed the decreased HSP60 and HSP70 while increased DDX1. X2K Appyter predicted the top ten transcription factors as key upstream regulators of the altered proteome. KEGG enrichment analysis revealed that these altered proteins were primarily associated with translational regulation, ribosome, cell cycle regulation, and cellular senescence. GO enrichment showed that focal adhesion, the structure where cells maintain cell interior-ECM interactions, was markedly overrepresented. Accordingly, functional validations demonstrated that SNAI1-overexpressed cells displayed aberrant ribosome biogenesis, indicated by increasing nucleophosmin and the nucleolar organizer regions. SNAI1-overexpressed cells exhibited senescent phenotypes including cell enlargement and increased granularity, up-regulated senescent makers p21 and γH2AX, and enhanced MMP-9 secretion. Moreover, SNAI1-overexpressed cells up-regulated paxillin, a scaffold protein located at focal adhesions crucial for their dynamic regulation. These findings provide insights into the molecular processes governed by snail1 during renal tubular cells undergoing EMT.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Kidney

DISEASE(S): Renal Fibrosis

SUBMITTER: Visith Thongboonkerd  

LAB HEAD: Prof. Visith Thongboonkerd

PROVIDER: PXD061033 | Pride | 2026-04-27

REPOSITORIES: Pride

Dataset's files

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Action DRS
670228_swp_human.FASTA Fasta
SNAI_1-1.raw Raw
SNAI_1-2.raw Raw
SNAI_1-3.raw Raw
SNAI_2-1.raw Raw
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Publications

Deciphering the impact of <i>SNAI1</i> gene on renal tubular cell proteome, nucleolar stress, ribosome biogenesis, senescence, DNA damage response, and focal adhesion dynamics.

Kanlaya Rattiyaporn R   Nonthawong Kanokwan K   Suntivichaya Mueanchan M   Yoodee Sunisa S   Thongboonkerd Visith V  

Genes & diseases 20251110 4


Snail1, encoded by <i>SNAI1</i> gene, is an essential protein that regulates epithelial-mesenchymal transition, which leads to extracellular matrix accumulation and kidney fibrosis, but with unclear cellular and molecular mechanisms. This study compared the cellular proteome of <i>SNAI1</i>-overexpressed renal tubular cells with that of vector-control cells by label-free quantitative proteomics, followed by functional assessments using various assays. A total of 233 proteins showed significant c  ...[more]

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